Acta Biomaterialia最新文献

{"title":"A multifunctional nanosystem catalyzed by cascading natural glucose oxidase and Fe3O4 nanozymes for synergistic chemodynamic and photodynamic cancer therapy","authors":"Jiale Li ,&nbsp;Bo Li ,&nbsp;Feng Liu ,&nbsp;Ming Deng ,&nbsp;Ziying Zhang ,&nbsp;Yutao Ran ,&nbsp;Bing Wang","doi":"10.1016/j.actbio.2024.10.024","DOIUrl":"10.1016/j.actbio.2024.10.024","url":null,"abstract":"<div><div>The significance of the tumor microenvironment (TME) in tumor initiation and progression is increasingly acknowledged. Conventional therapeutic approaches face limitations within the complex TME, including the restrictions imposed by hypoxia on photodynamic therapy (PDT) and the deficiency of endogenous H₂O₂ affecting chemodynamic therapy (CDT). In response to the TME's characteristics of high metabolism, hypoxia, and weak acidity, a multifunctional nanosystem MNPs/GOD@CS/IR820, which synergistically integrates CDT and PDT, has been developed. This system can actively accumulate at tumor sites under an external magnetic field and release active components in response to the weakly acidic TME. It mitigates the limitations imposed by hypoxia and endogenous H₂O₂ deficiency on PDT and CDT, respectively, thereby enabling synergistic treatment. Additionally, the system's multimodal imaging capabilities facilitate precise tumor localization and real-time, non-invasive <em>in vivo</em> assessment via fluorescence imaging and MRI. <em>In vitro</em> and <em>in vivo</em> evaluations demonstrate significant antitumor efficacy, effectively inhibiting tumor growth and improving survival rates. By comprehensively addressing the challenges posed by the complex TME and enhancing real-time monitoring capabilities, our nanosystem paves the way for personalized and precise cancer treatment.</div></div><div><h3>Statement of significance</h3><div>This study introduces an innovative MNPs/GOD@CS/IR820 nanosystem that represents a significant advancement in cancer nanomedicine by addressing critical limitations of conventional photodynamic therapy (PDT), particularly in hypoxic tumor microenvironments. By synergistically integrating chemodynamic therapy (CDT) with PDT and incorporating MRI and fluorescence dual-modal imaging capabilities, this multifunctional platform offers enhanced therapeutic efficacy and real-time monitoring. The system's ability to generate oxygen in situ overcomes hypoxia-induced limitations, while its multimodal mechanism of action induces tumor cell apoptosis through multiple pathways. In vitro and in vivo studies demonstrate remarkable antitumor efficacy across diverse cancer types, significantly inhibiting tumor growth and improving survival rates. This comprehensive approach to cancer diagnosis and treatment not only advances precision medicine for targeted, multimodal cancer management but also provides a promising foundation for future clinical applications, potentially transforming cancer treatment strategies and improving patient outcomes.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 518-530"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enzyme-responsive microgel with controlled drug release, lubrication and adhesion capability for osteoarthritis attenuation","authors":"Keyu Chen ,&nbsp;Jiachen Wang ,&nbsp;Jue Cao ,&nbsp;Fei Liu ,&nbsp;Jintao Fang ,&nbsp;Weixin Zheng ,&nbsp;Shubo Liu ,&nbsp;Yuexin Zhao ,&nbsp;Xintao Shuai ,&nbsp;Jinsheng Huang ,&nbsp;Bin Chen","doi":"10.1016/j.actbio.2024.10.026","DOIUrl":"10.1016/j.actbio.2024.10.026","url":null,"abstract":"<div><div>The treatment of osteoarthritis (OA) remains challenging due to the narrow therapeutic window and rapid clearance of therapeutic agents, even with intra-articular administration, resulting in a low treatment index. Recent advancements in local drug delivery systems have yet to overcome the issues of uncontrolled burst release and short retention time, leading to suboptimal OA treatment outcome. Herein, we developed a methacrylate-crosslinking hyaluronic acid (HA) microgel (abbreviated as CXB-HA-CBP) that covalently conjugates the anti-inflammatory drug celecoxib (CXB) via a metalloproteinase-2 (MMP-2)-responsive peptide linker (GGPLGLAGGC) and a collagen II binding peptide (WYRGRLC). The GGPLGLAGGC linker is specifically cleaved by the overexpressed MMP-2 enzyme within the OA joint, enabling the sustained and on-demand release of CXB entity. The synergistic action of CXB and HA effectively inhibited macrophage activation and reduced the production of pro-inflammatory cytokines, protecting chondrocytes from damage. Furthermore, the collagen II peptide introduced on the microgel surface enabled a cartilage-binding function to form an artificial lubrication microgel layer on the cartilage surface to reduce cartilage wear. The CXB-HA-CBP microgel showed an extended retention time of up to 18 days in the affected joint, leading to an effective OA treatment in rats. This sophistically designed microgel, characterized by the prolonged retention time, sustained drug delivery, and enhanced lubrication, presents a promising biomedicine for OA treatment.</div></div><div><h3>Statement of significance</h3><div>A new methacrylate-crosslinking hyaluronic acid (HA) microgel, covalently conjugated with the celecoxib (CXB)-GGPLGLAGGC and the collagen II binding peptide (CBP, peptide sequence: WYRGRLC), was developed. The overexpressed MMP-2 in OA joint cleaved the GGPLGLAGGC linker to trigger the CXB moiety release. Besides, the CBP on the surface of microgels enabled a cartilage-attaching ability, resulting in a prolonged retention time and an improved lubrication property in joint. This advanced drug-loading microgel remarkably reduced macrophage activation and pro-inflammation cytokine production, while protecting the chondrocytes via a dual action of CXB and HA. This study demonstrated that the enzyme-responsive drug-loading microgel could serve as an platform to efficiently attenuate osteoarthritis.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 191-204"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biocompatible chitin-based Janus hydrogel membranes for periodontal repair","authors":"Lin Huang ,&nbsp;Tao Wu ,&nbsp;Jing Sun ,&nbsp;Xinghuan Lin ,&nbsp;Yuhao Peng ,&nbsp;Rongrong Zhang ,&nbsp;Yang Gao ,&nbsp;Shuo Xu ,&nbsp;Yuxin Sun ,&nbsp;Yi Zhou ,&nbsp;Bo Duan","doi":"10.1016/j.actbio.2024.10.038","DOIUrl":"10.1016/j.actbio.2024.10.038","url":null,"abstract":"<div><div>Periodontal defects caused by severe periodontitis are a widespread issue globally. Guided tissue regeneration (GTR) using barrier membranes for alveolar bone repair is a common clinical treatment. However, most commercially available collagen barrier membranes are expensive and lack the antibacterial properties essential for effective bone regeneration. Herein, we report a natural polysaccharide chitin hydrogel barrier membrane with a Janus structure (ChT-PDA-p-HAP), featuring high antibacterial and protein-repelling activity on the outer side and good osteogenesis ability on the inner side. This multifunctional membrane is fabricated though a three-step process: (i) dissolution and regeneration of chitin, (ii) co-deposition with polydopamine (PDA) and poly(sulfobetaine methacrylate) (pSBMA), and (iii) coating with gelatin-hydroxyapatite (gelatin-HAP). In vitro cell experiments demonstrated the membrane's high biocompatibility and significant osteogenic activity. In vivo implantation in rats with periodontal defects revealed that the cemento-enamel junction index of the ChT-PDA-p-HAP membrane (1.165 mm) was superior to that of the commercial Bio-Gide® membrane (1.350 mm). This work presents a method for fabricating a chitin-based Janus barrier membrane, potentially expanding the use of chitin in tissue engineering.</div></div><div><h3>Statement of significance</h3><div>This study introduces a Janus hydrogel membrane based on chitin, tailored for guided tissue regeneration in periodontal defects. By combining antibacterial properties and osteogenic capabilities in a single membrane, the ChT-PDA-p-HAP membrane represents a significant advancement over traditional collagen barriers. Its outer surface, enhanced by Cu²⁺ and PDA-pSBMA coatings, resists bacterial colonization and protein adhesion effectively, while the inner side, coated with gelatin-HAP, promotes robust bone formation. In vitro experiments demonstrate high biocompatibility and substantial osteogenic differentiation, while in vivo testing in rat models confirms good therapeutic efficacy compared to commercial membranes. This multifunctional approach not only utilizes chitin's abundant natural resource but also integrates simple coating techniques to enhance therapeutic outcomes in periodontal tissue engineering, offering promising avenues for broader biomedical applications.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 219-232"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514417","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxygen-generating hydrogels combined with electrical stimulation: A dual approach for promoting diabetic wound healing","authors":"Taishan Liu ,&nbsp;Linlin Qu ,&nbsp;Chenhui Zhu ,&nbsp;Mengdi Guo ,&nbsp;Xiaoxuan Ma ,&nbsp;Huan Lei ,&nbsp;Daidi Fan","doi":"10.1016/j.actbio.2024.10.049","DOIUrl":"10.1016/j.actbio.2024.10.049","url":null,"abstract":"<div><div>Chronic wounds resulting from hyperglycemia and hypoxia are common complications in diabetic patients, posing significant challenges for clinical treatment. In this study, we developed a hydrogel (PVNP-SP) using [VBIM]Br, NIPAM, PEGDA, and spirulina, which exhibited strong antioxidant properties. The incorporation of [VBIM]Br endowed the hydrogel with electrical conductivity, allowing it to activate voltage-gated ion channels under an external electric field, thereby promoting cell survival and migration. The hydrogel also enhanced cellular antioxidant capacity by providing sustained oxygenation, inhibiting HIF-1α nuclear translocation, and activating the Nrf2/HO-1 pathway. Notably, in a chronic wound model, the combined effects of oxygen production and electrical stimulation from the PVNP-SP hydrogel significantly reduced wound inflammation, promoted collagen deposition and angiogenesis, and facilitated early wound closure. This therapeutic strategy, which mitigates hypoxia while integrating electrical stimulation, offers a highly effective strategy for improving chronic wound healing in diabetic patients.</div></div><div><h3>Statement of significance</h3><div>Inspired by photoautotrophic organisms, we combined microalgae with a conductive hydrogel and we demonstrated the synergistic promotion of chronic wound healing by electrical stimulation combined with microalgae oxygen-producing hydrogel. The approach of combining microalgae hydrogel patches with electrical stimulation demonstrates the feasibility of delivering oxygen to tissues while combining electrical stimulation for synergistic tissue repair. The hydrogel is easy to fabricate and handle, and may be suitable for a variety of treatments, such as myocardial infarction, lower limb ischemia, and drug delivery. The potential applicability of this hydrogel in a variety of treatments suggests that it has promising applications in regenerative medicine.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 95-106"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro-structural and micro-mechanical characterization of rock-boring angelwing clams","authors":"Yumeng Zhao,&nbsp;Sheng Dai","doi":"10.1016/j.actbio.2024.10.007","DOIUrl":"10.1016/j.actbio.2024.10.007","url":null,"abstract":"<div><div>Rock-boring behavior is a common phenomenon among certain bivalve clams, yet the mechanisms enabling this capability remain elusive. This study delves into the microstructural and micromechanical properties of the shells and denticles of angelwing (<em>Cyrtopleura costata</em>), a rock-boring clam. X-ray Diffraction Analysis and Energy-dispersive Spectroscopy identify that angelwing shells are made of pure aragonite. Scanning Electron Microscope images reveal that angelwing shells are mostly made of submicrometer-thick lamellar sheets, which are packed closely forming crossed-lamellar groups. Nanoindentation tests yield Young’s Moduli of <span><math><mrow><mn>30</mn><mo>−</mo><mn>70</mn><mspace></mspace><mi>G</mi><mi>P</mi><mi>a</mi></mrow></math></span> and hardness of <span><math><mrow><mn>3</mn><mo>−</mo><mn>10</mn><mspace></mspace><mi>G</mi><mi>P</mi><mi>a</mi></mrow></math></span> at different parts of the shells, making angelwing clam shells among the hardest biological materials. Further numerical simulations validate that the crossed-lamellar microstructure excels in withstanding external loads and safeguarding the integrity of the shell through minimized stress concentration.</div></div><div><h3>Statement of significance</h3><div>Boring and drilling in rocks are important for construction, energy, and scientific exploration. Nature offers ideas for improving these techniques, as seen in the rock-boring angelwing clam. Our study focuses on the mechanical and micro-structural properties of the clam’s shell, which help it bore into rocks. Through nanoindentation, we found that the clam’s shell is one of the hardest and stiffest biological shells, a key factor in its boring ability. We also identified intricate shell structures that likely enhance its strength and resistance to mechanical stress. These findings highlight important bio-material traits that could inspire new, more efficient drilling technologies for human use.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 423-434"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482765","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A bio-inspired Janus hydrogel patch facilitates oral ulcer repair by combining prolonged wet adhesion and lubrication","authors":"Yiqun Zhang ,&nbsp;Lingyuan Liu ,&nbsp;Xinghui Yu ,&nbsp;Hui Rong ,&nbsp;Wenjuan Chen ,&nbsp;Jianhua Zhang ,&nbsp;Anjie Dong ,&nbsp;Zujian Feng ,&nbsp;Shuangyang Li","doi":"10.1016/j.actbio.2024.10.041","DOIUrl":"10.1016/j.actbio.2024.10.041","url":null,"abstract":"<div><div>Oral ulcers, the most common type of mucosal lesion, are both highly prevalent and prone to recurrence. In the persistently moist environment of the oral cavity, current therapeutic patches face challenges such as short adhesion time, disruption by food particles and bacteria, and oral movements. To address these challenges, we develop a Janus patch, named ANSB, inspired by the multi-layered and asymmetric structure of natural mucosa, featuring a long-lasting adhesive layer and a lubricating layer. By eliminating the salivary barrier and leveraging covalent crosslinking between tissue surface amine groups and N-hydroxysuccinimide ester (NHS), the adhesive layer—composed of gelatin and acrylic acid—achieves rapid (≤ 30 s), strong (≥ 45 kPa), and durable (≥ 8 h) adhesion to wet buccal tissues. Furthermore, the efficient lubricating effect (COF = 0.02 ± 0.003) provided by zwitterions renders the lubricating layer of ANSB highly similar to natural mucosal tissue, effectively preventing bacterial invasion, secondary damage, and unintended adhesion. Additionally, the strong interlayer bonding and complementary mechanical properties are confirmed, resulting in a unified performance characterized by rapid wet adhesion, hydration lubrication, and enhanced mechanical strength. Importantly, ANSB treatment demonstrates a long-term protective barrier and superior therapeutic effects in rat oral ulcers, inhibiting pseudomembrane formation and accelerating tissue regeneration without causing secondary damage. Consequently, this distinctive Janus patch, characterized by prolonged adhesion, efficient lubrication, and simple preparation, holds significant potential for clinical oral ulcer treatment.</div></div><div><h3>Statement of Significance</h3><div>Oral ulcers, with healing impeded by secondary injury and bacterial invasion due to the absence of protective barriers, are highly prevalent and recurrent. However, sustaining therapeutic materials and physical barriers in the highly dynamic and moist oral environment poses a considerable challenge. In this study, a Janus patch (ANSB) that integrated a soft wet adhesive layer and a tough lubricating layer was developed to reconstruct a new protective barrier thus preventing external stimuli such as secondary damage and bacterial infiltration. This innovative patch with high therapeutic potential for oral ulcers may offer a new way for ulcer treatment based on barrier protection.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 120-132"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142549452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Age-related changes in the biochemical composition of the human aorta and their correlation with the delamination strength","authors":"Tomáš Suchý ,&nbsp;Lukáš Horný ,&nbsp;Monika Šupová ,&nbsp;Tomáš Adámek ,&nbsp;Alžběta Blanková ,&nbsp;Margit Žaloudková ,&nbsp;Martina Grajciarová ,&nbsp;Olena Yakushko ,&nbsp;Tereza Blassová ,&nbsp;Martin Braun","doi":"10.1016/j.actbio.2024.11.002","DOIUrl":"10.1016/j.actbio.2024.11.002","url":null,"abstract":"<div><div>Various studies have correlated the mechanical properties of the aortic wall with its biochemical parameters and inner structure. Very few studies have addressed correlations with the cohesive properties, which are crucial for understanding fracture phenomena such as aortic dissection, i.e. a life-threatening process. Aimed at filling this gap, we conducted a comprehensive biochemical and histological analysis of human aortas (the ascending and descending thoracic and infrarenal abdominal aorta) from 34 cadavers obtained post-mortem during regular autopsies. The pentosidine, hydroxyproline and calcium contents, calcium/phosphorus molar ratio, degree of atherosclerosis, area fraction of elastin, collagen type I and III, alpha smooth muscle actin, vasa vasorum, vasa vasorum density, aortic wall thickness, thicknesses of the adventitia, media and intima were determined and correlated with the delamination forces in the longitudinal and circumferential directions of the vessel as determined from identical cadavers. The majority of the parameters determined did not indicate significant correlation with age, except for the calcium content and collagen maturation (enzymatic crosslinking). The main results concern differences between enzymatic and non-enzymatic crosslinking and those caused by the presence of atherosclerosis. The enzymatic crosslinking of collagen increased with age and was accompanied by a decrease in the delamination strength, while non-enzymatic crosslinking tended to decrease with age and was accompanied by an increase in the delamination strength. As the rate of calcification increased, the presence of atherosclerosis led to the formation of calcium phosphate plaques with higher solubility than the tissue without or with only mild signs of atherosclerosis.</div></div><div><h3>Statement of significance</h3><div>This study presents a detailed biochemical and histological analysis of human aortic samples (ascending thoracic aorta, descending thoracic aorta and infrarenal abdominal aorta) taken from 34 cadavers. The contribution of this scientific study lies in the detailed biochemical comparison of the enzymatic and non-enzymatic glycosylation-derived crosslinks of vascular tissues and their influence on the delamination strength of the human aorta since, to the best of our knowledge, no such comprehensive studies exist in the literature. A further benefit concerns the notification of the limitations of the various analytical methods applied; an important factor that must be taken into account in such studies.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 344-361"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142607574","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glia in tissue engineering: From biomaterial tools to transplantation","authors":"AS Dill-Macky ,&nbsp;EN Lee ,&nbsp;JA Wertheim ,&nbsp;KM Koss","doi":"10.1016/j.actbio.2024.10.017","DOIUrl":"10.1016/j.actbio.2024.10.017","url":null,"abstract":"<div><div>Glia are imperative in nearly every function of the nervous system, including neurotransmission, neuronal repair, development, immunity, and myelination. Recently, the reparative roles of glia in the central and peripheral nervous systems have been elucidated, suggesting a tremendous potential for these cells as novel treatments to central nervous system disorders. Glial cells often behave as ‘double-edged swords’ in neuroinflammation, ultimately deciding the life or death of resident cells. Compared to glia, neuronal cells have limited mobility, lack the ability to divide and self-renew, and are generally more delicate. Glia have been candidates for therapeutic use in many successful grafting studies, which have been largely focused on restoring myelin with Schwann cells, olfactory ensheathing glia, and oligodendrocytes with support from astrocytes. However, few therapeutics of this class have succeeded past clinical trials. Several tools and materials are being developed to understand and re-engineer these grafting concepts for greater success, such as extra cellular matrix-based scaffolds, bioactive peptides, biomolecular delivery systems, biomolecular discovery for neuroinflammatory mediation, composite microstructures such as artificial channels for cell trafficking, and graft enhanced electrical stimulation. Furthermore, advances in stem cell-derived cortical/cerebral organoid differentiation protocols have allowed for the generation of patient-derived glia comparable to those acquired from tissues requiring highly invasive procedures or are otherwise inaccessible. However, research on bioengineered tools that manipulate glial cells is nowhere near as comprehensive as that for systems of neurons and neural stem cells. This article explores the therapeutic potential of glia in transplantation with an emphasis on novel bioengineered tools for enhancement of their reparative properties.</div></div><div><h3>Statement of significance</h3><div>Neural glia are responsible for a host of developmental, homeostatic, and reparative roles in the central nervous system but are often a major cause of tissue damage and cellular loss in insults and degenerative pathologies. Most glial grafts have employed Schwann cells for remyelination, but other glial with novel biomaterials have been employed, emphasizing their diverse functionality. Promising strategies have emerged, including neuroimmune mediation of glial scar tissues and facilitated migration and differentiation of stem cells for neural replacement. Herein, a comprehensive review of biomaterial tools for glia in transplantation is presented, highlighting Schwann cells, astrocytes, olfactory ensheating glia, oligodendrocytes, microglia, and ependymal cells.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 24-49"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure-function of cartilage in osteoarthritis: An ex-vivo correlation analysis between its structural, viscoelastic and frictional properties","authors":"Luisa de Roy ,&nbsp;Graciosa Quelhas Teixeira ,&nbsp;Jonas Schwer ,&nbsp;Matthias Sukopp ,&nbsp;Martin Faschingbauer ,&nbsp;Anita Ignatius ,&nbsp;Andreas Martin Seitz","doi":"10.1016/j.actbio.2024.10.027","DOIUrl":"10.1016/j.actbio.2024.10.027","url":null,"abstract":"<div><div>Healthy articular cartilage is characterized by extremely low friction and high compressive stiffness. This dual-functionality is tailored by its biphasic structure, whereby a fluid phase interacts with the extracellular matrix. Osteoarthritis (OA) causes structural changes, thereby altering the biomechanical and frictional properties. How the structural and functional properties of human cartilage are associated with OA remain unknown. To address this, we identified relationships between structural parameters, viscoelastic and frictional properties of degenerated human cartilage through correlation analyses. We found that cartilage friction was mainly influenced by its microscopic structure, while the viscoelastic properties were also related to the macroscopic structure. The viscoelastic and frictional properties displayed a weak correlation. These findings provide insights into the interplay between cartilage structure and its functional properties in OA, which might provide a basis for advancements in diagnosing and treating degenerated human cartilage.</div></div><div><h3>Statement of significance</h3><div>Osteoarthritis causes changes in the cartilages biphasic structure, thereby affecting functionality by altered biomechanical and frictional properties. Currently a cartilage-preserving therapeutic option remains lacking, because the disease is not fully understood. In our correlation analyses, we investigated relationships between the structural, the viscoelastic and frictional properties of degenerated human cartilage. We found that cartilage friction was particularly dependent on the microscopic structure, while the viscoelastic properties also correlated with the macroscopic structure. The frictional properties displayed only a weak dependency with the viscoelastic properties. These new insights into the structure-function and inter-functional relationships may provide new options to advance the diagnosis and treatment of degenerated cartilage.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 293-302"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142482778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A biodegradable lipid nanoparticle delivers a Cas9 ribonucleoprotein for efficient and safe in situ genome editing in melanoma","authors":"Xiaopeng Yang ,&nbsp;Songli Zhou ,&nbsp;Jingyi Zeng ,&nbsp;Suqin Zhang ,&nbsp;Meng Li ,&nbsp;Feifan Yue ,&nbsp;Zhaoyi Chen ,&nbsp;Yanming Dong ,&nbsp;Yingchun Zeng ,&nbsp;Jingwen Luo","doi":"10.1016/j.actbio.2024.10.030","DOIUrl":"10.1016/j.actbio.2024.10.030","url":null,"abstract":"<div><div>The development of melanoma is closely related to Braf gene, which is a suitable target for CRISPR/Cas9 based gene therapy. CRISPR/Cas9-sgRNA ribonucleoprotein complexes (RNPs) stand out as the safest format compared to plasmid and mRNA delivery. Similarly, lipid nanoparticles (LNPs) emerge as a safer alternative to viral vectors for delivering the CRISPR/Cas9-sgRNA gene editing system. Herein, we have designed multifunctional cationic LNPs specifically tailored for the efficient delivery of Cas9 RNPs targeting the mouse Braf gene through transdermal delivery, aiming to treat mouse melanoma. LNPs are given a positive charge by the addition of a newly synthesized polymer, deoxycholic acid modified polyethyleneimine (PEI-DOCA). Positive charge enables LNPs to be delivered <em>in vivo</em> by binding to negatively charged cell membranes and proteins, thereby facilitating efficient skin penetration and enhancing the delivery of RNPs into melanoma cells for gene editing purposes. Our research demonstrates that these LNPs enhance drug penetration through the skin, successfully delivering the Cas9 RNPs system and specifically targeting the Braf gene. Cas9 RNPs loaded LNPs exert a notable impact on gene editing in melanoma cells, significantly suppressing their proliferation. Furthermore, in mice experiments, the LNPs exhibited skin penetration and tumor targeting capabilities. This innovative LNPs delivery system offers a promising gene therapy approach for melanoma treatment and provides fresh insights into the development of safe and effective delivery systems for Cas9 RNPs <em>in vivo</em>.</div></div><div><h3>Statement of significance</h3><div>CRISPR/Cas9 technology brings new hope for cancer treatment. Cas9 ribonucleoprotein offers direct genome editing, yet delivery challenges persist. For melanoma, transdermal delivery minimizes toxicity but faces skin barrier issues. We designed multifunctional lipid nanoparticles (LNPs) for Cas9 RNP delivery targeting the Braf gene. With metal microneedle pretreatment, our LNPs effectively edited melanoma cells, reducing Braf expression and inhibiting tumor growth. Our study demonstrates LNPs' potential for melanoma therapy and paves the way for efficient <em>in vivo</em> Cas9 RNP delivery systems in cancer therapy.</div></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":"190 ","pages":"Pages 531-547"},"PeriodicalIF":9.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142514416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}